IgG anti-transglutaminase autoantibodies in systemic lupus erythematosus and Sjögren syndrome.

To the Editor: In a recent issue of this journal, van der Sluijs Veer and Vermes (1 ) reported a high prevalence and concentration of IgG anti-tissue transglutaminase (anti-tTG) antibodies in patients with systemic lupus erythematosus (SLE) and increased antidsDNA antibodies, as well as in anti-SSA/SSB-positive patients. No increase was observed in patients with other autoantibodies, such as anti-Sm/RNP, anti-nucleolar, antihistidyl-tRNA synthetase, anti-centromere protein B, anti-topoisomerase I, anti-proteinase 3, and IgM rheumatoid factor, or in patients with chronic inflammation. The authors proposed that in situations involving an imbalance between the supply and clearance of apoptotic bodies (as demonstrated in SLE), the immune system may detect intracellular tTG-substrate protein complexes, leading to an autoimmune response against the substrate and/or the tTG. Moreover, they argued that the difference in IgG anti-tTG concentrations between the SLE or antiSSA/SSB-positive groups and the other autoimmune disease groups could probably depend on a different pathogenetic mechanism, and they concluded that IgG anti-tTG determination in anti-dsDNA-positive SLE or anti-SSA/SSB-positive patients might provide additional clinical information and have clinical value in the monitoring of these individuals. In response to a subsequent comment by Di Tola et al. (2 ), these same authors reported that when they used a recombinant tTG prepared in a baculovirus system as antigen, no positivity for IgG anti-tTG was observed, whereas these autoantibodies were detected when they used a guinea pig extract. Our findings lend further support to this point, which may be diagnostically relevant. In a large study designed to assess anti-tTG prevalence in autoimmune diseases other than celiac disease, we performed IgA and IgG anti-tTG autoantibody assays in 750 individuals, including 100 SLE and 100 Sjögren patients (85% anti-SSA positive, 53% anti-SSB positive), using a human recombinant antigen (rhEu-tTG; Eurospital). Only one SLE patient was positive for IgA anti-tTG (celiac disease was subsequently confirmed by intestinal biopsy), and only two SLE and one Sjögren patient had IgG antitTG antibody concentrations above the cutoff (42, 46, and 61 kilounits/L, respectively; reference value, 30 kilounits/L). These three patients are currently under investigation to determine whether their original autoimmune disease is associated with celiac disease. The mean IgG antitTG antibody values in patients with SLE (20.9 6.8 kilounits/L) or Sjögren syndrome (11.9 7.0 kilounits/L) were not significantly different from those observed in healthy individuals (16.8 3.6 kilounits/L; P, not significant, Mann– Whitney test). The results of our study confirm those obtained (and not yet published) by van der Sluijs Veer and Vermes when they used a recombinant antigen rather than the native antigen extracted from guinea pig liver (3 ). Many positive IgG anti-tTG cases detected by use of extractive substrates are most likely false positives directed against contaminating antigens or tTG-substrate proteins (e.g., actin, keratin, histones, myosin, troponin, or tubulin). Indeed, antibodies to these proteins are also detectable in other autoimmune diseases in which, like SLE and Sjögren syndrome, marked B-polyclonal activation is present (4 ). Thus, our data and those of van der Sluijs Veer and Vermes clearly show that the use of antigen extracted from guinea pig liver may be the cause of false-positive reactions, especially in samples from patients with autoimmune disease; indeed, the more recent diagnostic methods that use human recombinant antigens not only are equally sensitive, but also guarantee greater specificity.